Fasting/re-feeding before initiation enhances the growth of aberrant crypt foci induced by azoxymethane in rat colon and rectum

Abstract

In contrast to the protective effect of chronic caloric restriction on tumor development, we have shown that fasting sustained tumor initiation in rat liver by a non‐initiating dose of diethylnitrosamine. Here we investigated whether fasting had a similar favorable effect on initiation in the colorectal mucosa in 80 male F344 rats. Animals fasted for 4 days were given a single s.c. dose of azoxymethane (AOM) (20 mg/kg) on the first day of re‐feeding, and rates of kinetic proliferative parameters, and development of the pre‐neoplastic lesions such as aberrant crypt foci (ACF), were evaluated. Starvation before AOM treatment enhanced the growth of ACF, as shown by the significantly higher crypt multiplicity of fasted/re‐fed rats as compared with fully fed rats (3.97 ± 0.50 vs. 2.64 ± 0.20, p ≤ 0.025). This difference was associated with perturbations in cell death and cell proliferation. Fasting induced apoptosis and depressed cell division, while re‐feeding had opposite effects, resulting in a higher percentage of S‐phase cells at the time of AOM injection and 2 days thereafter. Starvation‐induced apoptosis may represent the mitogenic stimulus to an increase in the number of cells susceptible to AOM damage, and may favor its fixation, leading to enhanced growth of ACF. Our data therefore suggest that fasting/re‐feeding enhances colon cancer. Int. J. Cancer 77:286–294, 1998.© 1998 Wiley‐Liss, Inc.

Get the Fat Out!

“…First, VF removal was an effective mode of suppressing experimental intestinal carcinogenesis, and it improved the animal survival rates similarly to CR. The beneficial effect of CR was in line with the previously reported experimental data that a calorie-rich diet augments colorectal carcinogenesis, whereas CR reduces colorectal tumor incidence (18, 19). The suppression of carcinogenesis induced by caloric restriction was likely associated with the morphological and biochemical changes in adipocytes.…”

Fasting and cancer: molecular mechanisms and clinical application

“…Furthermore, it is essential to apply FMDs with an understanding of the mechanisms of action, since their potency if applied incorrectly could generate negative effects. For example, when rats were fasted and treated with a potent carcinogen before refeeding, this resulted in the growth of aberrant foci in liver, colon and rectum when compared with non-fasted rats 151,152 . Although the mechanisms involved in this effect are not understood, and these foci may have not resulted in tumours, these studies suggest that a minimum period of 24–48 hours between the chemotherapy treatment and the return to the normal diet is important to avoid combining the regrowth signals present during the refeeding after fasting with high levels of toxic drugs such as chemotherapy.…”

Fasting Cycles Retard Growth of Tumors and Sensitize a Range of Cancer Cell Types to Chemotherapy

“…A period of fasting after chemotherapy treatment may be particularly important because chemotherapy drugs can cause DNA damage that could lead to secondary tumors and other toxicities. The combination of refeeding after fasting and treatment with potent carcinogens can enhance the growth of aberrant foci in liver, colon, and rectum (28, 29), probably because prolonged fasting can cause cell death and atrophy in organs such as the liver, and the cell proliferation induced by refeeding (to reestablish normal organ size) can lead to DNA damage if high concentrations of toxins are still present. Although chemotherapy drugs are not potent carcinogens and toxicity to multiple organs after fasting is reduced, not increased, even when refeeding is initiated immediately after chemotherapy (10-12), the length of the time period of fasting after chemotherapy should be based on the half-life of the chemotherapy drug to minimize toxicity to normal cells when refeeding begins.…”